Updated S2 K guidelines for the management of bullous pemphigoid initiated by the European Academy of Dermatology and Venereology (EADV).

BACKGROUND: Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disease of the skin and mucous membranes. This disease typically affects the elderly and presents with itch and localized or, most frequently, generalized bullous lesions. A subset of patients only develops excoriations, prurigo-like lesions, and eczematous and/or urticarial erythematous lesions. The disease, which is significantly associated with neurological disorders, has high morbidity and severely impacts the quality of life. OBJECTIVES AND METHODOLOGY: The Autoimmune blistering diseases Task Force of the European Academy of Dermatology and Venereology sought to update the guidelines for the management of BP based on new clinical information, and new evidence on diagnostic tools and interventions. The recommendations are either evidence-based or rely on expert opinion. The degree of consent among all task force members was included. RESULTS: Treatment depends on the severity of BP and patients' comorbidities. High-potency topical corticosteroids are recommended as the mainstay of treatment whenever possible. Oral prednisone at a dose of 0.5 mg/kg/day is a recommended alternative. In case of contraindications or resistance to corticosteroids, immunosuppressive therapies, such as methotrexate, azathioprine, mycophenolate mofetil or mycophenolate acid, may be recommended. The use of doxycycline and dapsone is controversial. They may be recommended, in particular, in patients with contraindications to oral corticosteroids. B-cell-depleting therapy and intravenous immunoglobulins may be considered in treatment-resistant cases. Omalizumab and dupilumab have recently shown promising results. The final version of the guideline was consented to by several patient organizations. CONCLUSIONS: The guidelines for the management of BP were updated. They summarize evidence- and expert-based recommendations useful in clinical practice.

Experimental airborne transmission of porcine postweaning multisystemic wasting syndrome.

The objective of these studies was to investigate if porcine postweaning multisystemic wasting syndrome (PMWS) could be induced in healthy pigs following contact with air from pigs with clinical signs of PMWS. The pigs were housed in different units. Either 31 (study I) or 25 (study II) pigs with clinical symptoms of PMWS from a PMWS-affected herd and 25 healthy pigs from a PMWS-free, but PCV2-positive, herd were housed in unit A. Fifty pigs from a PMWS-free herd were housed in unit B, which were connected by pipes to unit A. In unit C, 30 pigs from a PMWS-free herd were housed as controls. In study II, the pigs in units A and B from the PMWS-free herd developed clinical signs of PMWS 2-3 weeks after arrival. PMWS was confirmed at necropsy and the diseased pigs had increased PCV2 load and increased antibody titers against PCV2 in serum that coincided with the development of clinical signs typical of PMWS. Sequence analysis revealed that the PCV2 isolate belonged to genotype 2b. In conclusion, the present study showed that PMWS can be induced in pigs from a PMWS-free herd by airborne contact with pigs from a PMWS-affected herd.

Corticobasal and ataxia syndromes widen the spectrum of C9ORF72 hexanucleotide expansion disease.

Recently, a hexanucleotide (GGGGCC) repeat expansion in the first intron of C9ORF72 was reported as the cause of chromosome 9p21-linked frontotemporal dementia-amyotrophic lateral sclerosis (FTD-ALS). We here report the prevalence of the expansion in a hospital-based cohort and associated clinical features indicating a wider clinical spectrum of C9ORF72 disease than previously described. We studied 280 patients previously screened for mutations in genes involved in early onset autosomal dominant inherited dementia disorders. A repeat-primed polymerase chain reaction amplification assay was used to identify pathogenic GGGGCC expansions. As a potential modifier, confirmed cases were further investigated for abnormal CAG expansions in ATXN2. A pathogenic GGGGCC expansion was identified in a total of 14 probands. Three of these presented with atypical clinical features and were previously diagnosed with clinical olivopontocerebellar degeneration (OPCD), atypical Parkinsonian syndrome (APS) and a corticobasal syndrome (CBS). Further, the pathogenic expansion was identified in six FTD patients, four patients with FTD-ALS and one ALS patient. All confirmed cases had normal ATXN2 repeat sizes. Our study widens the clinical spectrum of C9ORF72 related disease and confirms the hexanucleotide expansion as a prevalent cause of FTD-ALS disorders. There was no indication of a modifying effect of the ATXN2 gene.

Infection dynamics of Lawsonia intracellularis in pig herds.

Little information is known about the natural course and within-herd prevalence of porcine proliferative enteropathy caused by Lawsonia intracellularis. The objective of the study was to investigate the within-herd dynamics of naturally acquired L. intracellularis infection in pigs from weaning to slaughter. The study was designed as a longitudinal survey where 100 pigs from five herds were randomly selected at weaning (approximately 4 weeks of age). Every second week until slaughter (10-12 times, i.e. 20-24 weeks) the pigs were weighed and faecal as well as blood samples were collected. Faecal shedding of L. intracellularis was assessed by real time-PCR and sero-conversion by an indirect immunofluorescence antibody test (IFAT). Clinical disease was not reported but infection was present in all herds and the PCR assay indicated infection in 75% of pigs examined. Most L. intracellularis infected pigs were shedding at 10-12 weeks of age (22-29 kg) and shed for 2-6 successive weeks. After 18 weeks of age all shedding had ceased and re-infection at PCR detectable level was not seen. Variable L. intracellularis associated impact on growth rate was observed. Immediately before bacterial shedding and during early infection the average growth rate declined whereas a compensatory impact was observed during later infection and after bacterial shedding had ceased. The performance of the IFAT resembled the bacteriological test almost perfectly. Sero-conversion was first detected at 12-14 weeks of age. Relative to the bacterial shedding, the onset of sero-conversion was a little delayed, in general, most pigs had sero-converted 2 weeks after the first shedding. Once sero-converted, 92% of the pigs remained sero-positive over the entire survey period.

Influence of light-dark schedules and stocking density on behaviour, risk of leg problems and occurrence of chronic fear in broilers.

1. The aims of this study were to determine (1) the effect of light-dark schedules on the walking ability, the risk of tibial dyschondroplasia (TD) as well as the duration of tonic immobility (TI) reactions in commercial broiler flocks and (2) the effect of a daily dark period and reduced density on the behaviour of broiler chickens. 2. Experiment 1. Group 1 had a 2 to 8 h daily dark period from 2 to 26 d of age (light-dark programme A) at a stocking density of 28.4 chicks/m2. Group 2 had 8 h of darkness daily from 2 to 38 d of age (light-dark programme B) at 24 chicks/m2. The control group had 24 h continuous light at 28.4 chicks/m2. 3. Experiment 2. Behaviour was studied with and without a daily 8 h dark period and at high (30 chicks/m2) and low (18 chicks/m2) stocking densities. 4. Programme B reduced the prevalence of impaired walking ability, corresponding to gait score > 2, when compared with controls. The effect on walking ability corresponding to gait score > 0 approached significance. 5. Both light-dark programmes reduced the occurrence of TD. Programme B (combined with reduced stocking density), however, had the greater effect. 6. Both light-dark programmes reduced the duration of TI, compared with controls (mean = 426 s) Programme B resulted in a larger reduction (alpha = -156.9 s) than programme A (alpha = -117.0). 7. The proportions of chicks drinking, eating, pecking, scratching, standing and performing vertical wing-shakes increased--both when the 8 h dark period and the reduced stocking density were applied separately and in combination (experiment 2). 8. For all behaviours, except standing, the effect of the dark period was largest in broilers kept at the high stocking density (d 40).

Lamotrigine for central poststroke pain: a randomized controlled trial.

OBJECTIVE: Central poststroke pain (CPSP) is usually difficult to treat. Amitriptyline, the only oral preparation shown to be effective in a randomized controlled trial, is often associated with a range of side effects related to the many mechanisms of actions of tricyclic antidepressants. We investigated the effect of lamotrigine, a drug that reduces neuronal hyperexcitability, on poststroke pain. METHODS: Thirty consecutive patients with CPSP (median age 59 years, range 37 to 77; median pain duration 2.0 years, range 0.3 to 12) from two centers participated in a randomized, double-blind, placebo-controlled cross-over study. The study consisted of two 8-week treatment periods separated by 2 weeks of wash-out. The primary endpoint was the median value of the mean daily pain score during the last week of treatment while treated with 200 mg/d lamotrigine. Secondary endpoints were median pain scores while on lamotrigine 25 mg/d, 50 mg/d, and 100 mg/d; a global pain score; assessment of evoked pain; areas of spontaneous pain; and allodynia/dysesthesia. RESULTS: Lamotrigine 200 mg/d reduced the median pain score to 5, compared to 7 during placebo (p = 0.01) in the intent-to-treat population of 27 patients. No significant effect was obtained at lower doses. Twelve patients (44%) responded to the treatment. There was a uniform tendency to reduction of all secondary outcome measures, but lamotrigine only had significant effects on some of the secondary outcome measures. Lamotrigine was well tolerated with few and transient side effects. Two mild rashes occurred during lamotrigine treatment, one causing withdrawal from study. CONCLUSIONS: Oral lamotrigine 200 mg daily is a well tolerated and moderately effective treatment for central poststroke pain. Lamotrigine may be an alternative to tricyclic antidepressants in the treatment of CPSP.

Influence of zinc bacitracin, light regimen and dustbathing on the health and welfare of broiler chickens.

1. The influence of zinc bacitracin, an antibiotic growth promoter, and the combined influence of two environmental factors (8 h of darkness and access to sand) on health and welfare variables were studied in 96 broiler chickens (kept as pairs). 2. Chickens fed with zinc bacitracin (ZB) had a higher frequency of tibial dyschondroplasia (TD) and a higher frequency of dustbathing than chickens fed without zinc bacitracin. 3. When 42 d old, chickens exposed to 8 h of darkness and access to sand were heavier than chickens reared under continuous light and with no access to sand. 4. Fluctuating asymmetry was higher in the 'light/no sand' groups than in the 'night/sand + ZB' group. 5. There was a negative correlation between tonic immobility and weight and a positive correlation between weight and TD.

Development of dustbathing behavior sequences in the domestic fowl: the significance of functional experience.

The development of the sequential structure of dustbathing bouts was studied in domestic egg-layer chicks from hatching until 23 days of age using a first order Markov chain model analysis. Chicks were reared either with access to sand ("sand chicks ") or on a wire floor ( "wire chicks"). All chicks in both groups developed a basic structure of the elements pecking, bill raking, ground scratching, vertical wingshaking, head rubbing, and side rubbing. Nonetheless, there was more cohesion in the bouts of sand chicks than in those of wire chicks: wire chicks had more pauses in their bouts and performed more elements while standing; also, allopecking (feather-pecking) and preening were incorporated into their bouts. We conclude that the basic structure of dustbathing bouts develops even in the absence of functional experience with feedback from sand. However, absence of normal feedback can lead to problems consisting of interruptions and feather-directed behavior.

Relationships between leg disorders and changes in the behaviour of broiler chickens.

The relationships between the severity of lameness, the presence of tibial dyschondroplasia, and the frequency of dustbathing behaviour and duration of tonic immobility were studied in 96 broiler chicks kept from day-old in groups of four in wire-floored cages. Dustbathing was observed when the birds were given access for one hour to a tray containing sand or straw. The duration of tonic immobility and the severity of lameness were scored during weeks 3, 4, 5 and 6. After slaughter at 41 or 45 days of age the birds were examined for tibial dyschondroplasia; 34 birds were classified as having tibial dyschondroplasia and 54 had detectable lameness problems. Birds with tibial dyschondroplasia had a higher lameness score (P < 0.001), dustbathed on fewer days (P < 0.0001), and had longer periods of tonic immobility (P < 0.03) at six weeks than birds which did not have the condition. However, almost all the chicks, including those with tibial dyschondroplasia dustbathed on day 27 after they had not been given access to the tray for three days, significantly more than on days when they had not been deprived of the tray (P < 0.0001). Furthermore, lame birds and birds with tibial dyschondroplasia also dustbathed less with age. Studies of the vertical wing-shaking element of dustbathing confirmed that tibial dyschondroplasia reduced dustbathing (P < 0.05) and also showed that during the one-hour tests, sand resulted in more dustbathing than straw (P < 0.01).

Development of social behaviour in four litters of dogs (Canis familiaris).

The development of social behaviour in 4 litters of dogs was observed without interfering with the puppies from birth to 8 weeks of age. Direct and continuous observation was combined with video recording. Three of the litters were observed during one session of 2 h once a week, and the fourth litter during one session of 40 min twice a week. Social interactions were divided into 1) investigation of litter mates (licking, sniffing or investigating orally), 2) social play, 3) and interactions in which agonistic elements (dominance postures, threats, bites or submission) were displayed. The different forms of social interactions appeared for the first time when the puppies were between 14 and 21 days of age. Social investigation appeared first and was followed by play and agonistic interactions. From week 5, differences between the puppies in the tendency to initiate social play and agonistic interactions emerged. Generally, within the litters individual differences were consistent over weeks 6-8 (positive correlations between weeks), whereas the tendency in the puppies during these weeks were negatively correlated with those of week 3 (play) or weeks 3 and 4 (agonistic interactions), indicating a rebound effect for both play and agonistic behaviour. No significant correlations, however, were found for social investigation. More often than expected males played or engaged in agonistic with other males, whereas these behaviours occurred less often than expected between females. Both males and females, however, preferred male partners for agonistic interactions. No sex differences were found in the direction of social investigation. Agonistic behaviour was often responded to by play and play was often responded to by agonistic behaviour, and the results indicated that before 8 weeks of age differences in social behaviour between the puppies were already established.

Development of a new production system for weaned and growing pigs.

The design of modem housing systems for farm animals calls for cooperation between scientists within different disciplines. This article describes the design of a new production system for weaned and growing pigs, as well as the analyses and working processes behind its development. The aim of the study was to develop an economically competitive system that also provided better welfare for the animals and a healthier environment for the workers. Analyses were carried out with emphasis on behavioral needs and building design and economy. The resulting system, the "safari system," consists of a number of straw flow pens of increasing size. Pigs are moved to larger and larger pens each week until slaughter. The main advantage is that pigs are not mixed during the growth period and that they are given more space, especially toward the end of the growth period when their space demand is high. Furthermore, the provision of straw for comfort and exploration and of wallow basins for cooling in the pens for the larger pigs were considered significant welfare improvements. An analysis revealed that the safari system would be economically competitive in comparison to traditional intensive systems.

The stress of not being able to perform dustbathing in laying hens.

The stress of not being able to perform dustbathing was studied in small groups of laying hens. The birds were reared and kept for 2.5 years in cages with either sand ("sand birds") or wire floors ("wire birds"), and subsequently deprived of sand (sand birds) or given access to sand (wire birds). Before this change, wire birds had a higher incidence of unilateral wing/leg stretching and stereotypic pecking compared to sand birds; however, there was no difference in corticosterone concentrations. Deprivation of sand in the sand birds resulted in a total absence of dustbathing and in a significant increase in corticosterone concentrations. Although the wire birds dustbathed on the wire before the change of floors, there was a significant increase in the incidence of dustbathing after sand was provided, but no changes in the concentrations of corticosterone. Threats and allopecks decreased in the wire birds after access to sand, whereas no changes were found in the sand birds. Stereotypic pecks on feathers were absent in the sand birds, but were frequent in most of the wire birds both before and after they were given sand. Also, in the wire birds, all feather pecking (stereotypic and nonstereotypic) was positively correlated with the concentration of corticosterone, and this kind of pecking may, thus, be an expression of stress in laying hens. We conclude that the nonperformance of dustbathing behavior is associated with the experience of stress.

[Risk factors for depression after apoplexy]. / Risikofaktorer for depression efter apopleksi.

An unselected cohort of 285 stroke patients, median age 69 years, was studied for correlation between potential risk factors and the one-year incidence of post-stroke depression (PSD). The following factors correlated significantly to PSD a history of previous stroke, a history of previous depression, female gender, living alone and social distress pre-stroke. Further, social inactivity, decrease in social activity, pathological crying and intellectual impairment at one month but not functional outcome correlated to PSD. A multivariate regression analysis showed that intellectual impairment explained 42% of the variance of the mood score. Major depression was unrelated to lesion location. We conclude the etiology of PSD is a complex mixture of pre-stroke personal and social factors and stroke-induced social, emotional and intellectual handicap.

Dementia of depression or depression of dementia in stroke?

This study describes the correlation between changes in mood symptoms assessed by the Hamilton Depression Rating Scale (HDRS) and intellectual impairment assessed by the Brief Cognitive Rating Scale (BCRS) and Mattis Dementia Rating Scale (MDRS) in 166 unselected 1-year survivors after stroke, in whom post-stroke depression (PSD) has previously been described and validated. The course of intellectual impairment associated with PSD was compared with the course of intellectual impairment in non-PSD patients. In general, improvement in mood symptoms was correlated with an improvement in intellectual function. However, in 53 PSD patients improvement in intellectual performance was absent, despite the fact that the patients reported being significantly less distressed by dementia symptoms. Antidepressive medication did not lead to any improvement in MDRS score. No evidence was found to support the hypothesis of 'dementia of depression'. To the contrary, the findings indicate 'depression of dementia'.

Developmental stability in relation to population density and breed of chickens Gallus gallus.

Bilaterally symmetrical morphological characters with fluctuating asymmetry usually have small, random deviations from symmetry that reflect the ability of individuals to cope with genetic and environmental stress. A comparison of the level of fluctuating asymmetry in two fast-growing breeds (ScanBrid, Ross 208) with that of a slow-growing breed (La Belle Rouge) and wild jungle fowl from India revealed a positive relationship between growth rate and asymmetry. Fast-growing chickens kept at three densities (20, 24, and 28 chickens per square meter) revealed a positive association between fluctuating asymmetry and density. Large individuals generally had higher levels of fluctuating asymmetry than small individuals. Tonic immobility, which is often used as a measure of fearfulness, was weakly positively associated with the degree of fluctuating asymmetry (P < .05). Measures of fluctuating asymmetry may provide information on levels of stress experienced by domesticated animals.

Risk factors for post-stroke depression.

An unselected cohort of 285 stroke patients, median age 69 years, were studied for correlation between potential risk factors and the 1-year incidence of post-stroke depression (PSD). The following factors correlated significantly with PSD: a history of previous stroke, a history of previous depression, female gender, living alone and social distress prestroke. Further, social inactivity, decrease in social activity, pathological crying and intellectual impairment at 1 month but not functional outcome correlated to PSD. A multivariate regression analysis showed that intellectual impairment explained 42% of variance of mood score. Major depression was unrelated to lesion location. We conclude that etiology to PSD is a complex mixture of prestroke personal and social factors, and stroke induced social, emotional and intellectual handicap.

[Effective treatment of depression following apoplexy with citalopram]. / Effektiv behandling af depression efter apopleksi med citalopram.

The aim of the study was to investigate the efficacy and safety of the selective serotonin reuptake inhibitor citalopram in treating post-stroke depression. A six-week double-blind placebo-controlled trial was undertaken. Diagnosis and outcome were determined using the Hamilton Depression Scale, and unwanted effects were measured using the UKU side effect rating scale. Sixty-six consecutive depressed patients entered the trial 2-52 weeks post-stroke. They were assigned to equally sized treatment and placebo groups. The initial level of depression and demographic parameters were comparable in the two groups. Significantly greater improvement was seen in patients treated with citalopram (10-40 mg/day) for three and six weeks. Half of the 28 patients who entered the trial two to six weeks post-stroke recovered within a month, independent of the treatment given. This indicates a high degree of spontaneous recovery in the early phase after stroke. In contrast, placebo recovery was infrequent in patients who started treatment seven weeks or more post-stroke. No serious side effects related to the treatment were detected, those present being mild and usually transient. The trial demonstrates that the selective serotonin reuptake inhibitor citalopram offers an advantageous new treatment of post-stroke depression that is both safe and effective.

Post-stroke pathological crying: frequency and correlation to depression.

While pathological crying has classically been described as a disturbance of the motor concomitants of emotional affect that is unrelated to mood, recent studies indicate that there may in fact be a correlation. We therefore undertook a study of post-stroke pathological crying in relation to mood score/depression and lesion site in an unselected stroke population the first year following stroke. The study population comprised 211 patients with first ever stroke (median age 69 years, range 25-80). The patients were included in the study within 7 days of the onset of stroke, and follow-up examinations were made at 1 month, 6 months and 1 year. Computerized tomography brain scans were obtained on Days 5-10. The frequency of pathological crying was 14% at 1 month, 10% at 6 months and 11% at 1 year. The overall 1 year incidence was 19%. Pathological crying correlated significantly to mood score and post-stroke depression (p < 0.005), as well as to lesion size (p < 0.05), Barthel Index (p < 0.05), Motricity Index (p < 0.005) and intellectual impairment (p < 0.05), but not to lesion location, sex, age, history of stroke or depression, predisposing disease or social distress before the stroke incident Post-stroke pathological crying was common and persistent in 11% of patients at 1 year and correlated strongly to mood score and post-stroke depression. The indication for treatment of pathological crying is therefore further strengthened.

Incidence of post-stroke depression during the first year in a large unselected stroke population determined using a valid standardized rating scale.

This study describes the development of post-stroke depression (PSD) prospectively during the first year post-stroke in 285 unselected stroke patients. An appropriate unselected population-based control group without cerebral pathology is included for comparison. Psychiatric assessment with the Hamilton Depression Rating Scale (HDRS) was undertaken unmodified. PSD was defined as HDRS > or = 13. The one-year incidence of PSD among the 209 survivors able to communicate reliably at 1 month was 41%. Most cases develop within the first months following stroke (79%), the frequency of new cases of PSD at one year being 5%, a level comparable to that in the control group. Depressed and nondepressed stroke patients consistently scored 4 points greater on total HDRS than in the corresponding controls.

Effective treatment of poststroke depression with the selective serotonin reuptake inhibitor citalopram.

BACKGROUND AND PURPOSE: The aim of the study was to investigate the efficacy and safety of the selective serotonin reuptake inhibitor citalopram in treating poststroke depression, since available treatments are usually poorly tolerated. METHODS: A 6-week double-blind, placebo-controlled trial was undertaken. Diagnosis and outcome were determined using the Hamilton Depression Scale, and unwanted effects were measured using the UKU side effect rating scale. Sixty-six consecutive depressed patients from an unselected population of 285 stroke patients aged 25 to 80 years entered the trial 2 to 52 weeks after stroke. They were assigned to equally sized treatment and placebo groups. The initial level of depression was comparable in the two groups (mean baseline Hamilton Depression scores, 19.4 and 18.9, respectively). Demographic parameters were also comparable in the two groups. RESULTS: Significantly greater improvement was seen in patients treated with citalopram (10 to 40 mg/d) for 3 and 6 weeks, both when including all patients (intention-to-treat analysis, P < .05) and excluding patients who dropped out during the first 3 weeks (efficacy analysis, P < .005). Half of the 28 patients who entered the trial 2 to 6 weeks after stroke recovered within 1 month, independent of the treatment given. This indicates a high degree of spontaneous recovery in the early phase after stroke. In contrast, recovery was infrequent in placebo group patients who became depressed 7 weeks or more after stroke. No serious side effects related to the treatment were detected; those present were mild and usually transient. CONCLUSIONS: This trial demonstrates that the selective serotonin reuptake inhibitor citalopram offers an advantageous new treatment of poststroke depression that is both safe and effective.